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- Nilsson, Peter M, et al.
(author)
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New Antidiabetic Agents for the Treatment of Heart Failure in Hypertensive Patients
- 2024. - 2
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In: Hypertension and Heart Failure : Epidemiology, Mechanisms and Treatment - Epidemiology, Mechanisms and Treatment. - 2366-4614 .- 2366-4606. - 9783031393143 - 9783031393150 ; , s. 79-371
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Book chapter (peer-reviewed)abstract
- The development of newer glucose-lowering drugs for the treatment of type 2 diabetes in recent years, such as the SGLT-2 inhibitors and GLP-1 receptor agonists/analogues with well-documented clinical benefits from large trials, has influenced international guidelines. These drugs are able to reduce both macro- and microvascular events in patients with type 2 diabetes and to prevent worsening of diabetic nephropathy. One important aspect of these new drugs is also the ability to prevent or treat heart failure (HF) through improved cardiac metabolism, but also by lowering of blood pressure and improvement of central hemodynamics. In this review, the evidence for such effects on HF is discussed for each drug class separately and in combination. In the future there may come new opportunities for fixed drug combinations (FDC) to improve cost-effectiveness and compliance of diabetes treatment when antihypertensive, lipid-lowering, and glucose-lowering drugs are combined. As control of hypertension is of great importance for HF prevention in patients with diabetes in general, the combination of traditional antihypertensive drugs (i.e., blockers of the renin-angiotensin system) with newer glucose-lowering drugs that may also lower blood pressure could prove to be a successful and a very useful combination. Thus, further studies are warranted.
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- Padmanabhan, Sandosh, et al.
(author)
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Genome-Wide Association Study of Blood Pressure Extremes Identifies Variant near UMOD Associated with Hypertension
- 2010
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In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 6:10
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Journal article (peer-reviewed)abstract
- Hypertension is a heritable and major contributor to the global burden of disease. The sum of rare and common genetic variants robustly identified so far explain only 1%-2% of the population variation in BP and hypertension. This suggests the existence of more undiscovered common variants. We conducted a genome-wide association study in 1,621 hypertensive cases and 1,699 controls and follow-up validation analyses in 19,845 cases and 16,541 controls using an extreme case-control design. We identified a locus on chromosome 16 in the 59 region of Uromodulin (UMOD; rs13333226, combined P value of 3.6x10(-11)). The minor G allele is associated with a lower risk of hypertension (OR [95% CI]: 0.87 [0.84-0.91]), reduced urinary uromodulin excretion, better renal function; and each copy of the G allele is associated with a 7.7% reduction in risk of CVD events after adjusting for age, sex, BMI, and smoking status (H.R. = 0.923, 95% CI 0.860-0.991; p = 0.027). In a subset of 13,446 individuals with estimated glomerular filtration rate (eGFR) measurements, we show that rs13333226 is independently associated with hypertension (unadjusted for eGFR: 0.89 [0.83-0.96], p = 0.004; after eGFR adjustment: 0.89 [0.83-0.96], p = 0.003). In clinical functional studies, we also consistently show the minor G allele is associated with lower urinary uromodulin excretion. The exclusive expression of uromodulin in the thick portion of the ascending limb of Henle suggests a putative role of this variant in hypertension through an effect on sodium homeostasis. The newly discovered UMOD locus for hypertension has the potential to give new insights into the role of uromodulin in BP regulation and to identify novel drugable targets for reducing cardiovascular risk.
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- Rosberg, Victoria, et al.
(author)
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Simple cardiovascular risk stratification by replacing total serum cholesterol with anthropometric measures : The MORGAM prospective cohort project
- 2022
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In: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 26
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Journal article (peer-reviewed)abstract
- To assess whether anthropometric measures (body mass index [BMI], waist-hip ratio [WHR], and estimated fat mass [EFM]) are independently associated with major adverse cardiovascular events (MACE), and to assess their added prognostic value compared with serum total-cholesterol. The study population comprised 109,509 individuals (53% men) from the MORGAM-Project, aged 19–97 years, without established cardiovascular disease, and not on antihypertensive treatment. While BMI was reported in all, WHR and EFM were reported in ∼52,000 participants. Prognostic importance of anthropometric measurements and total-cholesterol was evaluated using adjusted Cox proportional-hazards regression, logistic regression, area under the receiver-operating-characteristic curve (AUCROC), and net reclassification improvement (NRI). The primary endpoint was MACE, a composite of stroke, myocardial infarction, or death from coronary heart disease. Age interacted significantly with anthropometric measures and total-cholesterol on MACE (P ≤ 0.003), and therefore age-stratified analyses (<50 versus ≥ 50 years) were performed. BMI, WHR, EFM, and total-cholesterol were independently associated with MACE (P ≤ 0.003) and resulted in significantly positive NRI when added to age, sex, smoking status, and systolic blood pressure. Only total-cholesterol increased discrimination ability (AUCROC difference; P < 0.001). In subjects < 50 years, the prediction model with total-cholesterol was superior to the model including BMI, but not superior to models containing WHR or EFM, while in those ≥ 50 years, the model with total-cholesterol was superior to all models containing anthropometric variables, whether assessed individually or combined. We found a potential role for replacing total-cholesterol with anthropometric measures for MACE-prediction among individuals < 50 years when laboratory measurements are unavailable, but not among those ≥ 50 years.
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- Stergiou, George, et al.
(author)
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Bedtime dosing of antihypertensive medications: systematic review and consensus statement : International Society of Hypertension position paper endorsed by World Hypertension League and European Society of Hypertension
- 2022
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In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 40:10, s. 1847-1858
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Research review (peer-reviewed)abstract
- Antihypertensive drug therapy is one of the most efficient medical interventions for preventing disability and death globally. Most of the evidence supporting its benefits has been derived from outcome trials with morning dosing of medications. Accumulating evidence suggests an adverse prognosis associated with night-time hypertension, nondipping blood pressure (BP) profile and morning BP surge, with increased incidence of cardiovascular events during the first few morning hours. These observations provide justification for complete 24-h BP control as being the primary goal of antihypertensive treatment. Bedtime administration of antihypertensive drugs has also been proposed as a potentially more effective treatment strategy than morning administration. This Position Paper by the International Society of Hypertension reviewed the published evidence on the clinical relevance of the diurnal variation in BP and the timing of antihypertensive drug treatment, aiming to provide consensus recommendations for clinical practice. Eight published outcome hypertension studies involved bedtime dosing of antihypertensive drugs, and all had major methodological and/or other flaws and a high risk of bias in testing the impact of bedtime compared to morning treatment. Three ongoing, well designed, prospective, randomized controlled outcome trials are expected to provide high-quality data on the efficacy and safety of evening or bedtime versus morning drug dosing. Until that information is available, preferred use of bedtime drug dosing of antihypertensive drugs should not be routinely recommended in clinical practice. Complete 24-h control of BP should be targeted using readily available, long-acting antihypertensive medications as monotherapy or combinations administered in a single morning dose.
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- Vishram, Julie K.K., et al.
(author)
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Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage : a LIFE substudy
- 2015
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In: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 33:12, s. 2422-2430
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Journal article (peer-reviewed)abstract
- Background: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH).Methods: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP=630 events).Results: In multiple regression models adjusted for mean BP6-24months and treatment allocation, neither high BP6-24months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24months SD and range (both b=0.04, P<0.01). Independently of mean BP6-24months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24months SD [hazard ratio per 1mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P=0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P=0.004), SBP6-24months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P=0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P=0.04). Adjusted for the same factors, stroke was associated with DBP6-24months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P=0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P=0.001), SBP6-24months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P=0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P=0.05), but MI was not.Conclusion: In LIFE patients, higher in-treatment BP6-24months variability was independently of mean BP6-24months associated with later CEP and stroke, but not with MI or TOD after 24 months.
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- Zannad, Faiez, et al.
(author)
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Prevention of cardiovascular disease guided by total risk estimations - challenges and opportunities for practical implementation: highlights of a CardioVascular Clinical Trialists (CVCT) Workshop of the ESC Working Group on CardioVascular Pharmacology and Drug Therapy.
- 2012
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In: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4873 .- 2047-4881. ; 19:6, s. 1454-1464
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Research review (peer-reviewed)abstract
- This paper presents a summary of the potential practical and economic barriers to implementation of primary prevention of cardiovascular disease guided by total cardiovascular risk estimations in the general population. It also reviews various possible solutions to overcome these barriers. The report is based on discussion among experts in the area at a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy that took place in September 2009. It includes a review of the evidence in favour of the 'treat-to-target' paradigm, as well as potential difficulties with this approach, including the multiple pathological processes present in high-risk patients that may not be adequately addressed by this strategy. The risk-guided therapy approach requires careful definitions of cardiovascular risk and consideration of clinical endpoints as well as the differences between trial and 'real-world' populations. Cost-effectiveness presents another issue in scenarios of finite healthcare resources, as does the difficulty of documenting guideline uptake and effectiveness in the primary care setting, where early modification of risk factors may be more beneficial than later attempts to manage established disease. The key to guideline implementation is to improve the quality of risk assessment and demonstrate the association between risk factors, intervention, and reduced event rates. In the future, this may be made possible by means of automated data entry and various other measures. In conclusion, opportunities exist to increase guideline implementation in the primary care setting, with potential benefits for both the general population and healthcare resources.
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